SUMMARY Erosive tooth wear (ETW) is a multifactorial and cumulative condition of growing prevalence that leads to substantial loss of dental structure, resulting in pain and harm to dental function and esthetics. Specifically in the USA, it affects approximately 46% of teenagers and 80% of adults. Despite these alarming numbers, USA dental professionals are largely unaware of this condition, and specific diagnostic set rules and management guidelines are non-existent. Currently, the clinical assessment and monitoring of ETW is done by visual examination using subjective indices. The long-term goal of this study is to develop a non-invasive and non- destructive clinical assessment for the detection, differentiation and monitoring of ETW progression. This assessment will be based on the clinical measurement of enamel thickness and dental surface texture by polarization-sensitive optical coherence tomography (PS-OCT) and white-light scanning confocal profilometry (WLSCP), respectively. The hypothesis to be investigated is that the combination of surface texture and enamel thickness analyses can provide objective and reliable information for the diagnosis and monitoring of ETW. The rationale for the proposed research is that the studied objective clinical outcomes will allow the early diagnosis and monitoring of ETW, preventing its progression to advanced stages, when the required treatments to restore the anatomy, function and esthetics of the affected dentition are complex and costly. Guided by preliminary data, the hypothesis will be tested by pursuing two specific aims: 1. To investigate PS- OCT and WLSCP parameters for the detection and monitoring of simulated ETW lesions in controlled intra-oral conditions; 2. To investigate the use of PS-OCT and WLSCP for the detection and monitoring of natural ETW lesions clinically. In Aim 1, the proposed outcomes will be tested using an intra-oral experimental model accounting for the effects of chemical, biological and behavioral factors involved in the development of ETW. In Aim 2, a clinical longitudinal study will be performed on adult patients presenting higher risk for ETW lesion development, due to dry-mouth condition. Enamel thickness and surface texture parameters will be evaluated on specific locations of pre-determined teeth, as well as a previously validated questionnaire aiming to identify ETW risk factors. Evaluations will be performed at baseline and after 3, 6, 9 and 12 months. The proposed research is significant, because it will provide the basis for the development of an objective clinical assessment protocol to diagnose and monitor ETW development, identifying its relation to biological and behavioral factors. This will also open new avenues for the development and testing of novel and more clinically efficacious treatments for ETW.